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Literature summary extracted from

  • Luu, W.; Zerenturk, E.J.; Kristiana, I.; Bucknall, M.P.; Sharpe, L.J.; Brown, A.J.
    Signaling regulates activity of DHCR24, the final enzyme in cholesterol synthesis (2014), J. Lipid Res., 55, 410-420 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.3.1.72 ectopic expression of wild-type and mutant human DHCR24s in CHO-7 cells that are deficient for DHCR24 through specific siRNA knockout, quantitative real-time RT-PCR enzyme expression analysis Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
1.3.1.72 T110A site-directed mutagenesis, mutation and inactivation of the phosphorylation site results in 60% loss of activity compared to wild-type Homo sapiens
1.3.1.72 T110E site-directed mutagenesis, DHCR24 activity of the phosphomimetic T110E mutant is similar to wild-type activity Homo sapiens
1.3.1.72 Y299F site-directed mutagenesis, compared with wild-type DHCR24, the mutant Y299F stable cells contain reduced DHCR24 mRNA expression while having comparable DHCR24 protein levels, the mutant enzyme activity is reduced by 40% compared to the wild-type Homo sapiens
1.3.1.72 Y300F site-directed mutagenesis, compared with wild-type DHCR24, the mutant Y299F stable cells contain comparable DHCR24 mRNA expression while having reduced DHCR24 protein levels, the mutant enzyme activity is similar to the wild-type Homo sapiens
1.3.1.72 Y321F site-directed mutagenesis, the mutant enzyme activity is similar to the wild-type Homo sapiens
1.3.1.72 Y507F site-directed mutagenesis, the mutant enzyme activity is reduced by 60% compared to the wild-type Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.3.1.72 additional information inhibitors of protein kinase C ablate DHCR24 activity, although not through a known phosphorylation site T110. PKC inhibitors, BIM and Ro-318220, reduce cholesterol levels and accumulate desmosterol within 4 h, indicating decreased DHCR24 activity Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.3.1.72 cholesta-5,24-dien-3beta-ol + NADPH + H+ Homo sapiens reduction of desmosterol to cholesterol is dependent on FAD cholest-5-en-3beta-ol + NADP+
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.3.1.72 Homo sapiens Q15392
-
-

Posttranslational Modification

EC Number Posttranslational Modification Comment Organism
1.3.1.72 phosphoprotein protein kinase C (PKC) activates DHCR24 activity through reversible phosphorylation. PKC inhibitors, BIM and Ro-318220, reduce cholesterol levels and accumulate desmosterol within 4 h, indicating decreased DHCR24 activity. Phosphorylation at T110 modulates DHCR24 activity Homo sapiens

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.3.1.72 HeLa cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.3.1.72 cholesta-5,24-dien-3beta-ol + NADPH + H+ reduction of desmosterol to cholesterol is dependent on FAD Homo sapiens cholest-5-en-3beta-ol + NADP+
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.3.1.72 3beta-hydroxysterol DELTA24-reductase
-
 Homo sapiens
1.3.1.72 DHCR24
-
 Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
1.3.1.72 FAD DHCR24 contains a highly conserved FAD binding domain comprising amino acids 111-203 Homo sapiens
1.3.1.72 NADPH DHCR24 activity is strictly dependent on NADPH Homo sapiens

Expression

EC Number Organism Comment Expression
1.3.1.72 Homo sapiens DHCR24 is transcriptionally regulated by sterols via the sterol-regulatory element-binding protein-2 transcription factor additional information

General Information

EC Number General Information Comment Organism
1.3.1.72 malfunction mutating residues T110, Y299, and Y507 of known phosphorylation sites inhibits DHCR24 activity. Seven missense mutations in DHCR24 have been described in desmosterolosis: R94H, R103C, E191K, N294T, K306N, Y471S, E480K. PKC inhibition results in desmosterol accumulation Homo sapiens
1.3.1.72 metabolism DHCR24 is the final enzyme in cholesterol synthesis, role of signaling in regulating cholesterol homeostasis Homo sapiens
1.3.1.72 physiological function the enzyme activity is regulated by signaling through kinases and reversible phosphorylation Homo sapiens